Positron Emission Tomography (PET) is a powerful tool for diagnosing a number of health related conditions and detection of disease. Generally, PET imaging systems create images based on the distribution of positron-emitter isotopes in the tissue of a subject. The isotopes are typically administered to the subject by injection of probe molecules that comprise a positron-emitter isotope (radioisotopes, radionuclides), such as [18F], [11C], [13N], or [15O], which are attached to a molecule that is readily metabolized or localized in the subject, e.g., glucose, or that chemically binds to receptors within the subject. In some cases, the isotope can be administered to the subject as a solution or by inhalation.
Generally, radioisotopes are produced by bombarding a target material with a particle beam of a particle accelerator, e.g., a cyclotron. Thereafter, the radioisotopes are radiochemically processed into one or more radio-labeled molecular imaging probes for subsequent introduction into the subject. A number of devices for producing and automatically radiochemically synthesizing molecular imaging probes are known, for example, the Eclipse® line of cyclotrons and Explora® line of radiochemical-synthesizing devices and are known and are commercially available from Siemens Medical Solutions USA, Inc. of Malvern, Pa. Other examples of cyclotron, radiochemical synthesizing devices, e.g., gas processing units, and components therefor are described in U.S. Pat. Nos. 6,011,825 and 6,599,484 and U.S. Pat. Pub. Nos. 2002/0028177, 2005/0084055, 2006/0285623, and 2007/0043213, which disclosures are incorporated herein by reference.
An important factor in the production of radio-labeled molecular imaging probes is specific activity. Specific activity of a radioisotope or molecular imaging probe is the amount of radioactivity relative to the mass of the radioisotope or molecular imaging probe, and is often measured in Ci/μmol. The mass consists of all isotopic forms of the radioactive label. Accordingly, the specific activity can be affected by known synthesis processes, for example, the addition of stable isotopes during processing can result in dilution, or lowering of specific activity.
By way of example, in the case of 18F the maximum specific activity is 1,710 Ci/μmol. [18F] fluoride ion produced by proton bombardment of a metal target filled with [18O] water in a cyclotron typically has a specific activity of about 50-100 Ci/μmol, which represents up to a 40 to 1 dilution with stable [19F] that is present in the [18O] water and released from the metal target body and polymeric valves and tubing of the target delivery system. In general, [18F] labeled molecular imaging probes prepared from [18F] fluoride ion have a specific activity of about 2-5 Ci/μmol after coupling of the [18F] ion to a probe molecule, which illustrates that the radiochemical synthesis process results in another 25 to 1 dilution with stable [19F]. Fluoride ion delivered from the cyclotron target will typically contain 0.2-0.4 μg (10-20 μmol) stable [19F] fluoride ion along with the radioactive [18F] fluoride ion. If the activity delivered is 1.0 Ci, the [18F] fluoride ion mass will be about 9.0 ng or 0.5 nmol.
Similar issues arise when using [11C] and other radioactive isotopes because known radiochemical synthesis processes are primary sources of unwanted [12C] and other stable isotopes. For example, the maximum specific activity of [11C] is 9,240 Ci/μmol. However, one current method of producing [11C]CO is involves passing a volume of gas, e.g. [11C]CO2, over a packed bed of carbon and copper granules. As a result, the [12C] carbon granules of the packed bed act as a source of contamination of the [11C]CO and ultimately reduce the specific activity.
Accordingly, there is a need for a method and device for producing radio-labeled molecular imaging probes, and more specifically [11C]CO and [15O]CO, which exhibit higher specific activities while maintaining the simplicity and ease of current known devices and methods.